During the past year, we have been focused on: 1) determining the high-resolution structure of the Rev response element (RRE) RNA; 2) developing new inhibitor targeting the HIV-1 viral RNA; 3) continuing the development of a technology for selective labeling of RNA molecules. We are working on production of the RRE RNA microcrystals suitable for XFEL experiments. Based on the structure that we have reported, we have developed a new class of inhibitors targeting the RRE RNA. The new inhibitors bind to the RRE RNA with at least 10-fold higher affinity than the viral Rev protein, the natural ligand of the RRE RNA. A provisional patent has been filed based on this study. We have used NMR, small angle X-ray scattering and single molecule Forster Resonance Engergy Transfer (smFRET) experiment to characterize the conformation space of the adenine riboswitch. Our results revealed that the binding pocket changed its conformation in response to ligand binding and that the distal loop-loop interaction of Adenine riboswitch aptamer restricts the conformational freedom of the three-way junction to promote ligand binding. Furthermore, the ligand binding also restricts the freedom of three-way junction to promote the distal loop-loop interaction under physiological conditions. These results provide an integrated view of hierarchical folding in atomic levels in an adenine riboswitch aptamer as a function of ligand and ion concentration. We are at the final stage of completing the project and have written the first draft of a manuscript to report the study. My group has developed a new method for selective labeling of RNA (SLOR) at designated residue(s) and/or segment(s) of large RNAs using solid-phase multi-cycle enzymatic reactions. Currently, we have filed a provisional patent for the SLOR technology and a draft of the manuscript has been written.